PROJECT SUMMARY/ABSTRACT The Center of Research Excellence in Natural Products Neuroscience (CORE-NPN) at The University of Mississippi School of Pharmacy (UM), initiated ten years ago through a COBRE grant, has developed a multidisciplinary team committed to evaluating the effects of natural products on the central nervous system (CNS). The Center now has the potential to develop and sustain an innovative and independently funded research center focused on treating disorders associated with the nervous system. Medicinal chemistry, drug metabolism, and pharmacokinetics (DMPK) are vital components of the iterative cycle of drug discovery, both embedded in hit-to-lead and lead optimization stages. The Chemistry/DMPK Research Core of the COBRE CORE-NPN program represents a shared core facility with the goal of serving biomedical investigators/users with consultation and specialized services and training in synthetic medicinal chemistry and DMPK as broadly defined within the NPN program. This Core is positioned to become a leader in synthesis, analysis, and early- stage DMPK evaluation of natural product and synthetic small-molecule drug discovery and development campaigns by accomplishing the following Specific Aims: (1) To strengthen the Chemistry/DMPK Research Core by providing users with enhanced services, access, and training in state-of-the-art instrumentation, specialized techniques, and scientific expertise; (2): To advance an infrastructure of developmental services to facilitate COBRE CORE-NPN research; (3): To accelerate a long-term plan for sustainability of the Core through expansion of the user base, research partnerships and collaborations, integration of a fee-for-service structure, institutional support, and adaptation to changes by monitoring the needs of the users. These aims will facilitate the transition of the Chemistry-DMPK Core into a fully self-sustained facility providing specialized research services and training opportunities essential in supporting investigators and bridging the drug discovery gap by providing users with consultation, training, and services in medicinal chemistry/DMPK, helping to alleviate the bottleneck associated with compound acquisition and evaluation.